*4.3. Telomeric Regions*

Telomeric and sub-telomeric regions in *T. cruzi* are sites of frequent DNA recombination that generate extensive genetic variations [73]. Therefore, they present a continuous evolutionary process. This concerns the relative abundance and organization of different genes, such as trans-sialidases, DGF-1 (dispersed gene family 1), RNA-helicases, RHS (retrotransposon hot spot genes), and N-acetyl-transferases [74,75]. In other protist parasites, as *T. brucei* or *Plasmodium falciparum*, sub-telomeric regions also present an important role in events of antigenic variation [76,77]. Trans-sialidase-like genes were located close to telomeric regions in *T. cruzi*, which generates new gene variations through non-homologous recombination. It was suggested that double-strand breaks produced in the sub-telomeric regions by retrotransposon nucleases are repaired by homologous recombination, but when the repair includes non-homologous chromatids there is a possibility to generate new gene variants [73]. This mechanism could contribute to the immune evasion of the parasite. Technically, it could also contribute to the collapsed assemblies of repetitive regions in sequencing. These sequences, the tandem repeats and/or other short repetitive genomic motifs, which correspond to telomeric and sub-telomeric regions, may produce an increment of fragmented genomes in *T. cruzi*, in comparison with other related species as *Leishmania* or *T. brucei*.
